Skip to main content
SpringerLink
Log in

Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10

  • Original Investigations
  • Published:
Human Genetics Aims and scope Submit manuscript

Abstract

A panel of glial tumors consisting of 11 low grade gliomas, 9 anaplastic gliomas, and 29 glioblastomas were analyzed for loss of heterozygosity by examining at least one locus for each chromosome. The frequency of allele loss was highest among the glioblastomas, suggesting that genetic alterations accumulate during glial tumor development. The most common genetic alteration detected involved allele losses of chromosome 10 loci; these losses were observed in all glioblastomas and in three of the anaplastic gliomas. In order to delineate which chromosome 10 region or regions were deleted in association with glial tumor development, a deletion mapping analysis was performed, and this revealed the partial loss of chromosome 10 in eight glioblastomas and two of the anaplastic gliomas. Among these cases, three distinct regions of chromosome 10 were indicated as being targeted for deletion: one telomeric region on 10p and both telomeric and centromeric locations on 10q. These data suggest the existence of multiple chromosome 10 tumor suppressor gene loci whose inactivation is involved in the malignant progression of glioma.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Bergerheim U, Nordenskjöld M, Collins VP (1989) Deletion mapping in human renal cell carcinoma. Cancer Res 49:1390–1396

    Google Scholar 

  • Bigner SH, Mark J, Burger RC, Mahaley Jr MS, Bullard DE, Mulbaier LH, Bigner DD (1988) Specific chromosomal abnormalities in malignant human gliomas. Cancer Res 48:405–411

    Google Scholar 

  • Bigner SH, Mark J, Bigner DD (1990) Cytogenetics of human brain tumors. Cancer Genet Cytogenet 47:141–154

    Google Scholar 

  • Bowden DW, Gravius TC, Green P, Falls K, Wurster-Hill D, Noll W, Müller-Kahle H, Donis-Keller H (1989) A genetic linkage map of 32 loci on human chromosome 10. Genomics 5:718–726

    Google Scholar 

  • Burger PC, Vogel FS, Green SB, Strike TA (1985) Glioblastoma multiforme and anaplastic astrocytoma: pathological criteria and prognostic implications. Cancer 56:1106–1111

    Google Scholar 

  • Carson NL, Simpson NE (1991) A physical map of human chromosome 10 and a comparison with an existing genetic map. Genomics 11:379–388

    Google Scholar 

  • Chung RY, Seizinger BR (1992) Molecular genetics of neurological tumors. J Med Genet 29:361–367

    Google Scholar 

  • Chung R, Whaley J, Kley N, Andersen K, Louis D, Menon A, Hettlich C, Freiman R, Hedley-White ET, Martuza R, Jenkins R, Yandell D, Seizinger BR (1991) TP53 gene mutations and 17p deletions in human astrocytomas. Genes Chrom Cancer 3:323–331

    Google Scholar 

  • Deimling A von, Eibl RH, Ohgaki H, Louis DN, Ammon K von, Petersen I, Kleihues P, Chung RY, Wiestier OD, Seizinger BR (1992) p53 mutations are associated with 17p allelic loss in grade II and grade III astrocytoma. Cancer Res 52:2987–2990

    Google Scholar 

  • Ekstrand AJ, Sugawa N, James CD, Collins VP (1992) Amplified and rearranged epidermal growth factor receptor genes in human glioblastomas reveal deletions of sequences encoding portions of the N and/or C-terminal tails. Proc Natl Acad Sci USA 89:4309–4313

    Google Scholar 

  • El-Azouzi M, Chung RY, Farmer GE, Martuza RL, Black McLP, Rouleau GA, Hettlich C, Hedley-Whyte ET, Zervas NT, Panagopoulos K, Nakamura Y, Gusella JF, Seizinger BR (1989) Loss of distinct regions on the short arm of chromosome 17 associated with tumorigenesis of human astrocytomas. Proc Natl Acad Sci USA 86:7186–7190

    Google Scholar 

  • Feinberg AP, Vogelstein BA (1983) A technique for radiolabeling DNA restriction endonuclease fragments to high specific activity. Anal Biochem 132:6–13

    CAS  PubMed  Google Scholar 

  • Frankel RH, Bayona W, Koslow M, Newcomb EW (1992) p53 mutations in human malignant gliomas: comparison of loss of heterozygosity with mutation frequency. Cancer Res 52:1427–1433

    Google Scholar 

  • Fujimoto M, Fults DW, Thomas GA, Nakamura Y, Heilbrun MP, White R, Story JL, Naylor SL, Kagen-Hallet KS, Sheridan PJ (1989) Loss of heterozygosity on chromosome 10 in human glioblastoma multiforme. Genomics 4:201–214

    Google Scholar 

  • Fults D, Tippets RH, Thomas GA, Nakamura Y, White R (1989) Loss of heterozygosity for loci on chromosome 17p in human malignant astrocytoma. Cancer Res 49:6572–6577

    Google Scholar 

  • Fults D, Pedone CA, Thomas GA, White R (1990) Allelotype of human malignant astrocytoma. Cancer Res 50:5784–5789

    Google Scholar 

  • Fults D, Brockmeyer D, Tullous MW, Pedone CA, Cawthon RM (1992) p53 mutation and loss of heterozygosity on chromosome 17 and 10 during human astrocytoma progression. Cancer Res 52:674–679

    Google Scholar 

  • Garson JA, McIntyre PG, Kemshead JT (1985) N-myc amplification in malignant astrocytoma. Lancet II:718–719

    Google Scholar 

  • James CD, Carlbom E, Dumanski JP, Hansen M, Nordenskjöld M, Collins VP, Cavenee WK (1988) Clonal genomic alterations in glioma malignancy stages. Cancer Res 48:5546–5551

    Google Scholar 

  • James CD, Carlbom E, Nordenskjöld M, Collins VP, Cavenee WK (1989) Mitotic recombination of chromosome 17 in astrocytomas. Proc Natl Acad Sci USA 86:2858–2862

    Google Scholar 

  • James CD, Mikkelsen T, Cavenee WK, Collins VP (1990) Molecular genetic aspects of glial tumour evolution. Cancer Surv 4:631–644

    Google Scholar 

  • James CD, He H, Carlbom E, Nordenskjöld M, Caveneee WK, Collins VP (1991) Chromosome 9 deletion mapping reveals interferon a and interferon β-1 gene deletions in human glial tumors. Cancer Res 51:1684–1688

    Google Scholar 

  • Kinzler KW, Bigner SH, Bigner DD, Trent JM, Law ML, O'Brien SJ, Wong AJ, Vogelstein B (1987) Identification of an amplified, highly expressed gene in human glioma. Science 236:70–73

    CAS  PubMed  Google Scholar 

  • Libermann TA, Nusbaum HR. Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J (1985) Amplification, enhanced expression, and possible rearrangement of the EGF receptor gene in primary human brain tumors of glial origin. Nature 313:144–147

    CAS  PubMed  Google Scholar 

  • Lindblom A, Skoog L, Ikedahl-Anderson T, Rotstein S, Nordenskjöld M, Larsson C (1993) Four separate regions of chromosome 17 show loss of heterozygosity in familial breast carcinomas. Hum Genet 91:6–12

    Google Scholar 

  • Nigro JM, Baker SJ, Preisinger AC, Jessup JM, Hostetter R, Cleary K, Bigner SH, Davidson N, Baylin S, Devilee P, Glover T, Collins FS, Weston A, Modali R, Harris CC, Vogelstein B (1989) Mutations in the p53 gene occur in diverse human tumour types. Nature 342:705–708

    Google Scholar 

  • Okazaki H, Scheithauer BW (1988) Atlas of neuropathology. Gower Medical Publishing New York

    Google Scholar 

  • Rasheed ABK, Fuller GN, Friedman AH, Bigner DD, Bigner SH (1992) Loss of heterozygosity for 10 loci in human gliomas. Genes Chrom Cancer 5:75–82

    Google Scholar 

  • Scherer HJ (1940) Cerebral astrocytomas and their derivates. Am J Cancer 40:159–198

    Google Scholar 

  • Sidransky D, Mikkelsen T, Schwechheimer K, Rosenblum ML, Cavenee W, Vogelstein B (1992) Clonal expansion of p53 mutant cells is associated with brain tumor progression. Nature 355:846–847

    Google Scholar 

  • Simpson NE. Cann HM (1991) Report of the committee on the genetic constitution of chromosome 10. Cytogenet Cell Genet 58:428–458

    Google Scholar 

  • Trent J, Meltzer P, Rosenblum M, Harsh G, Kinzler K, Mashal R, Feinberg A, Vogelstein B (1986) Evidence for rearrangement, amplification, and expression of c-myc in a human glioblastoma. Proc Natl Acad Sci USA 83:470–473

    Google Scholar 

  • Venter DJ, Bevan KL, Ludwig RL, Riley TEW, Jat PS, Thomas DGT, Noble MD (1991) Retinoblastoma gene deletions in human glioblastomas. Oncogene 6:445–448

    Google Scholar 

  • Watanabe K, Nagai M, Wakai S, Arai T, Kawashimi K (1990) Loss of constitutional heterozygosity in chromosome 10 in human glioblastoma. Acta Neuropathol 80:251–254

    Google Scholar 

  • White RL, Lalouel J-M, Nakamura Y, Donis-Keller H, Green P, Bowden DW, Mathew CGP, Easton DF, Robson EB, Morton NE, Gusella JF, Haines JL, Retief AE, Kidd KK, Murray JC, Lathrop GM, Cann HM (1990) The CEPH consortium primary linkage map of human chromosome 10. Genomics 6:393–412

    Google Scholar 

  • Williamson R, Bowkock A, Kidd K, Pearson P, Scmidtke J, Ceverha P, Chipperfield M, Cooper DN, Coutelle C, Hewitt J, Klinger K, Langley K, Beckmann J, Tolley M, Maidak B (1991) Report of the DNA committee and catalogues of cloned and mapped genes formated for PCR and DNA polymorphisms. Cytogenet Cell Genet 58:1190–1832

    Google Scholar 

  • Wu J, Myers S, Carson N, Kidd JR, Anderson L, Castiglione CM, Hoyle LS, Lichter JB, Sukhatme VP, Simpson NE, Kidd KK (1990) A refined linkage map for DNA markers around the pericentromeric region of chromosome 10. Genomics 8:461–468

    Google Scholar 

  • Ziilch KG (1979) Histological typing of tumors of the central nervous system. International histological classification of tumors, no. 21. World Health Organization, Geneva, Switzerland

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Clinical Genetics, Karolinska Hospital, Stockholm, Sweden

    A. Elisabeth Karlbom, Magnus Nordenskjöld & Catharina Larsson

  2. Department of Neurosurgery, Karolinska Hospital, Stockholm, Sweden

    A. Elisabeth Karlbom & Jürgen Boethius

  3. Department of Neurosurgery, Emory University, Atlanta, Georgia, USA

    C. David James

  4. Ludwig Institute for Cancer Research, San Diego, California, USA

    Webster K. Cavenee

  5. Department of Pathology, Sahlgrenska Hospital, University of Gothenburg, Sweden

    V. Peter Collins

  6. Ludwig Institute for Cancer Research, Karolinska Hospital, Stockholm, Sweden

    V. Peter Collins

Authors
  1. A. Elisabeth Karlbom
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C. David James
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jürgen Boethius
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Webster K. Cavenee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. V. Peter Collins
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Magnus Nordenskjöld
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Catharina Larsson
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Karlbom, A.E., James, C.D., Boethius, J. et al. Loss of heterozygosity in malignant gliomas involves at least three distinct regions on chromosome 10. Hum Genet 92, 169–174 (1993). https://doi.org/10.1007/BF00219686

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00219686

Keywords

Search

Navigation